Abstract

Glioblastoma multiform (GBM) is the most common, lethal and aggressive type of primary brain tumor. Despite the improvement of surgical and chemo/radiotherapeutic techniques, the prognosis for GBM is still poor, with median survival of 9-12 months. The occurrence of radio-resistance is one of the major obstacles to treat the GBM. Aberrant expression of miRNAs has been demonstrated to be involved in the initiation, progression, and metastasis of cancers. miRNA expression profiling studies revealed that a number of miRNA were dysregulated in GBM. Here, we investigated the potential role of miR-203, which is one of the downregulated miRNAs, in the modulation of radio-sensitivity in GBM. Transiently overexpressed miR-203 sensitized U251 malignant glioma cells to radiation concurrent with the downregulation of AKT activity. Overexpression of miR-203 prolonged radiation-induced γH2AX foci formation and downregulation of DNA-dependent protein kinases, suppressed invasion, migration potential and vasculogenic mimicry formation. In contrast, antisense-mediated inhibition of miR-203 expression results in decreased radio-sensitivity and features of Epithelial-Mesenchymal Transition (EMT). Taken together, our findings suggest that the miR-203 could be a useful target for overcoming the radio-resistance of GBM.